Answers courtesy of Dr Chris Jackson from South Australia (Sept 2003)

Queries – 8, 17, 28, 29, 32, 48, 66, 67, 73, 74, 91, 124, 129, 137, 168, 170, 177, 189, 208, 213, 218, 225, 269, 277

General Pharmacology MCQs

1. A drug is given at a dose of 50mg/kg to a 70kg man. The plasma concentration after giving it is 10mg/ml. The elimination half-life is 8 hours. Clearance would be:a. 1.3l/hrb. 3l/hrc. ?d. 125l/hre. ?Comment (PD): I have done this twice and I still get 0.03l/hr. I agree – Vd = dose / [ ] = 3500 mg / 10 mg/ml = 350 mlCl = 0.693 x Vd / t1/2 = 0.693 x 350 ml / 8 hrs = 30 ml / hr

Presumably something got lost in the translation…

2. A drug is given orally and 95% absorbed. Only 25% reached the general circulation due to hepatic first pass metabolism. If hepatic blood flow is 1500ml/min, the hepatic clearance is:a. 400ml/minb. ?c. 1100ml/mind. ?e. 1425ml/minHep clearance = HER x HBF = ((0.95 – 0.25)/0.95) x 1500 ml / min = 1105

3. Rectal administration of drugs:a. gives predictable blood levelsb. from lower 1/3 avoids first pass metabolism and upper 2/3 doesn’t Katzung 43 says 50%

- near enough as the others are wrongc. none undergoes firs pass metabolismd. all of it undergoes first pass metabolism

4. LD50 is:a. median lethal dose Katzung 30b. determined in phase 1 clinical trial – phase 0 in animals determines LD50; phase 1 in 20

– 100 healthy human volunteers determines basic pharmacokineticsc. determined from log-dose response curve this would seem to imply a graded curve – so A

is probably the best option.d. dose causing death in 50% animals with ?1/?4 hourse. half the mean lethal dose

5. Which of the following crosses the blood-brain barrier?a. GABAb. Propranolol c. Suxamethoniumd. Edrophoniume. Dopamine

6. With regard to drug-receptor binding:a. a competitive antagonist has no intrinsic activityb. a partial agonist has less receptor affinity than a full agonistc. KD is max intrinsic efficacy

7. A partial agonist:a. always antagonises a full agonistb. can never be used to antagonise a full agonistc. has a dose response curve similar to that of a full agonist in the presence of a non-

competitive antagonistd. ?

8. Placental transfer of drugs:a. increases in late pregnancy Wood and Woodb. increases late because of decreased albumin can’t find anything to support thisc. do not cross if MW > 600 daltons – no, lipid sol drugs cross with increasing difficulty up

to 1 000 Da (Katzung 1025)d. lipid soluble drugs diffuse through placenta depending on concentration gradient really

depends on flow on each side of membrane – ie placental perfusion (K 1026)e. increased diffusion if greater plasma protein binding in fetus true from first principles

9. Regarding pharmacokinetics:a. ?b. half-life is inversely proportional to clearance Cl = 0.693 x Vd / t1/2

c. ?d. half-life is proportional to steady statee. B & D

10. The NMDA receptor:a. ketamine is an agonist antagonistb. requires glycine as a modulating protein (“YES PROTEIN!”) to have its effect obviously

not a protein – a trapc. Mg blocks the receptor blocks the channeld. Is not permeable to calcium is, along with Na and K

11. Activated charcoal:a. should be given with sorbitol no b. is not effective against theophylline is effectivec. should be given with ipecac no – impairs charcoald. should be given in a drug:charcoal ratio of 1:10 ideally, yes (Dunn 537)

12. Therapeutic index:a. easy to determine in humans no!!b. ?c. ?d. ?e. derived from LD50/ED50 yentis 528

13. Oxygen toxicitya. causes convulsions at less than 100kPa no, Paul Bert convulsions at > 200kPa 100% O2 -

Nunn 505b. causes lipid peroxidation at less than 100kPa yes, mechanism of pulm toxicity at > 60%

FI O2 at 1 atm – Nunn 503

14. With regard to log-dose response curves:a. the response is fairly linear over the 20-80% range it’s the gradientb. the dose is fairly linear over the 20-80% range that’s near linearc. the ED50 and slope are characteristic for each drugd. ?e. ?

15. Zero order kinetics means:a. ?b. ?c. drug is eliminated at a constant rate regardless of dose yes, yentis 432d. elimination half-time will vary according to dose I can imagine this might be true – can’t

confirme. ?

Inhalational Anaesthetics MCQs

16. Which compound(s) is/are broken down in soda-lime?a. nitrous oxide nothing about this in Millerb. halothane alkaline hydrolysis – safe productsc. sevoflurane good ol’ cpd A – I’d choose this option out of these 5d. desflurane CO (D>E>I>S=H)e. all of the above

17. Regarding nitrous oxide at 70%a. synthetised from ? and N2 at 273C heat ammonium nitrate over water at 250 Cb. decreased muscle blood flow by 30% tends to slightly increase SVR – Miller 114c. decreases cerebral autoregulation by 24% very specific figure - ?source – but best of a

bad lot – how would you quantify it?d. ?

18. Nitrous oxide:a. ?increases/decreases CBF miller 710b. is an effective oxidant oxidises Co in methioninec. is made by heating nitrogen and oxygen in an iron retort nod. decreases pulmonary artery pressure in neonates no, increases PVR in all age groups,

perhaps in part because it inhibits NAdr uptake – note implications for R to L shunts – Miller 114 - 115

19. The following drugs are (potent) triggers for malignant hyperthermia EXCEPT:a. decamethonium ?probably yesb. suxamethoniumc. isofluraned. halothanee. calciumf. sevofluraneg. nitrous oxideh. tubocurarine 2 case reports(Different options on different papers)

20. IPPV with isoflurane at 1 MAC results in:a. depresses cardiovascular reflexes more than halothane no, H/E>Ib. causes decreased conduction velocity noc. maintains cerebral autoregulation yes – Stoelt 41, to 1.1 MAC isod. equal respiratory depression to enflurane no, E>I=D>S=He. reduction in cardiac output by 25% no, Peck 90 says a small decr CO (with HR up and

contractility down)f. increased vasodilatation yes

21. The effect of increased cardiac output on Pa versus time for volatile agents is:a. no effectb. decrease slopec. decrease then increase sloped. increase then decrease slope

22. nitrous oxide:a. supports combustionb. is flammable noc. causes muscle rigidity yes, Stoelting 65 - hyperbaricallyd. in tissues is slower to reabsorb than oxygen faster, I thinke. has a partition coefficient of 0.76 0.47f. all of the aboveg. is formed by heating oxygen and nitrogen noh. induces methionine synthetase inhibits iti. oxidises the cobalt in vitamin B12 yes

23. Nitrous oxide:a. has MW of 42 44b. critical temperature of 32C 36.5c. formed by using iron as a catalystd. does not support combustion doese. has saturated vapour pressure of 24kPaf. produced using ammonium sulphate in an iron retortg. boiling point 32C craph. ammonium nitrate ?? copper vessel ??(Multiple options as this represents 2 separate N2O questions on Mar 98 paper)

24. Desflurane:a. takes 5 minutes to reach equilibrium more like 10 minb. if fastest to approach equilibrium of any inhaled anaesthetic agent xenon and nitrous are

fasterc. is a fluorinated diethyl ether methyl ethyl etherd. ?none of these

25. Regarding sevoflurane: Miller 183-4a. the vapour pressure is less than enflurane S 160 E 175b. the vapour pressure is greater than isoflurane I 250c. cardiovascular side effects are similar to isoflurane nod. molecular weight is less than isoflurane >e. boiling point is greater than enflurane S 58.5 E 56.5

26. Sevoflurane:a. is a methylethyl ether methylisopropyl etherb. is odourlessc. is stable in soda lime at 37 degrees cpds A - Ed. has a boiling point higher than enfluranee. has a molecular weight lower than desflurane

27. Sevoflurane:a. molecular weight greater than enfluraneb. MAC less than enflurane S 2 E 1.68c. Contains Cl & F only Fd. SVP>enflurane

28. Uptake of N2O when breathing 70%a. more than one litre absorbed in the first minute 0.43 x 5 x 0.7 = 1.7 litres in first minute

– although on the web discussion board K Brandis said in fact it would be 1 litreb. equilibrium is achieved in 3 minutes noc. absorb 10 litres at time of 90% equilibrium in first 3 minutes poor wording but sounds

way too high Stoelt 25 – absorb up to 10 litres of N2O in first 10 – 15 minutes – watch the wording on the day

d. at steady state, uptake is 200ml/min no, this implies an 8% AV difference at FIN20 of 0.70 – would be less – aside from anything else this rapidity of uptake would render low flow anaesthesia with N2O more difficult

e. produces surgical anaesthesiamain point here is Severinghaus equation (Miller 87) – uptake = sol x CO x AV difference x proportion of inspired gas mix in 1st minute assume venous PP = 0, so uptake = sol x CO x PA (as a %)subsequently uptake = uptake in 1st minute x (time in min)0.5

29. N2O causes the second gas effect because:a. it is relatively insolubleb. reaches equilibrium faster than the more soluble second gas no – works with desc. larger volume c and d are pretty well synonymous – poor MCQ really – loss of volume

causes further influxd. higher concentration

30. Desflurane:a. is non-irritant to the airwaysb. is more/less potent than sevofluranec. has a higher molecular weight than ?isoflurane/?enflurane lighter than both as F < Cld. is a chlorinated methyl ethyl ether no Cl

31. Effects of volatile agents include:a. halothane increases hepatic artery and portal blood flowb. isoflurane causes hypotension by reducing cardiac outputc. ?d. ?neither – both H and I hep a and portal v graph Stoelt 57; I hep a much more, so

net effect HBF; H portal v more so net effect HBFiso causes BP by SVR

32. Problems with MAC:a. large interspecies variability true for some drugs eg Enf dog 2.58, humans 1.68b. affected by temperature and other factors yes eg hypo/hyperthermia in dogs – perhaps opt

for this as A less clinically relevant?c. affected by obesity nod. ?e.

33. MAC: Miller 1097a. is decreased in the elderlyb. is unchanged throughout pregnancy c. increases in hypothermia d. ?decreased/?increased with hyper/hypokalaemia no change

34. All these factors decrease MAC except:a. pregnancyb. hyperthermia c. hypothermiad. hypoxia no change unless very lowe. ?

35. MAC:a. Highest between ages 2-5 6/12 roughly – graph Stoelting 31b. Increases with pregnancy c. MAC BAR is concentration at which 95% do not move no – no HR/BP/NAdrd. Is 0.2% halothane in 70% N2O 0.29e. ?

36. With regards to MAC:a. the MAC of halothane with 70% N2O is 0.29b. concentration at which 95% of patients don’t move after a surgical stimulus 50%c. MAC-BARd. Decreased by increased CO2 no change – Miller 1097e. ?

37. Systemic vascular resistance is LEAST changed with:a. isoflurane b. sevoflurane c. desflurane d. enflurane e. halothane 0

38. MAC awake during emergence when patient will respond to command:a. 0.1b. 0.2c. 0.3 Miller 1095 – 0.37% iso = 0.37/1.15 MAC iso = 0.3 MAC iso d. 0.5e. 0.7

39. Isoflurane and enflurane are:a. structural isomersb. enantiomersc. diastereomersd. optical isomerse. configurational isomers

40. Sevoflurane:a. is broken down in the body to Compound A which has been shown to be toxic to ratsb. has a blood:gas partition coefficient of 2.3 0.7c. is an irritant causing coughing on inductiond. has a boiling point of 24 degrees centigradee. has Cl and F atoms in its structuref. none of the above

41. With isoflurane anaesthesia, MAC awake is:a. 0.1%b. 0.3%c. 0.4%0.37%d. 0.5%e. 1%

42. Isoflurane:a. is a halogenated methyl ethyl etherb. higher boiling point than sevoflurane I 48.5 S 58c. no odourd. enantiomer of enflurane

43. MAC of halothane with 70% N2O is:a. 0.25% 0.29% b. 0.5%c. 0.75%d. 1.0%e. ?

44. N2O is NOT relatively contra-indicated with:a. pneumothoraxb. ear surgeryc. post-op nausea and vomitingd. renal failure

45. Which of the following does NOT affect the speed of induction with a volatile agent?a. FRC by reservoir size for mixingb. Obesity though of course this does reduce FRC…c. PCO2 ie alveolar ventilationd. Cardiac output

46. Regarding the time constant for volatile anaesthetic uptake in the lungs:ie sol x CO x (PA – PV/Patm)

a. affected by agent concentration yes - PA b. affected by obesity yes - PV

c. not affected by FRC nod. affected by restrictive lung disease yes – c and d affect alveolar ventilatione. so how does all of the above sound?

47. 22g of Nitrous oxide at STP occupies a volume of:a. 3.6Lb. 11.2L ie half a molec. 22.4Ld. 44.1L

48. Wash in of volatile anaesthetics is reduced in neonates because:strongly disagree with premise here – wash in is accelerated in neonates because ratio of alveolar ventilation to FRC is greater

a. reduced FRCb. increased cardiac index true, CI is higher, but a greater proportion goes to VRG so faster

onset despite uptakec. decreased plasma protein levels irrelevantd. (something about blood;gas partition coefficients being different in neonate)Stoelting p

25 – blood gas coeffs lower: –18% for H,E,M,I but not S in neonates

49. The washout of inhalational anaesthetics: all truea. increases with elimination by the liver yes – metabolism augments washoutb. related considerably with the duration of anaesthesia yes – Miller 90c. increases in the neonate compared to the adult yes - accelerated in neonates because ratio

of alveolar ventilation to FRC is greater

50. With regard to compound A:a. increased production in Baralyme compared to sodalimeb. more likely in childrenc. sevofluranes metabolites cause hepatotoxicityd. sevoflurane is metabolised to compound A in the livere. ?

51. Concerning the effects of various volatile agents on cerebral blood flow under conditions of 1 MAC and normocarbia:

a. halothane produces greater increase than enfluraneb. isoflurane produces greater increase than enfluranec. any change produced depends upon cerebral metabolic rated. change in CBF is due to change in cardiac outpute. ? re C and D – change w H is because of cerebral vasodilation and loss of autoreg

52. Which of the following drugs is not associated with EEG epileptiform activity:a. propofol has caused seizures – Miller 252b. enfluranec. ?d. ?other options???e. ?

Intravenous Anaesthetics MCQs

53. Propofol:a. has a pKa of 7 11b. has a pH of 11 7c. causes hypotension due to myocardial depression SVR more than COd. has 98% protein binding

54. Thiopentone causes a decrease in BP by:a. direct decrease in myocardial contractilityb. fall in systemic vascular resistancec. decrease in venous tone immed post inductiond. ?

55. Ketamine:a. is a direct inotrope b. causes bronchodilatationc. less likely to see emergence delirium in younger females more likelyd. reduces pharyngeal secretions e. leaves airway reflexes reliably intact unreliable

56. With regard to the action of midazolam:a. ring closure occurs immediately on injection yes – physicochem change on exposure to

pHb. ?c. ?

57. Propofol depresses cardiac output predominantly by:a. direct depression of myocardial contractilityb. decreased SVRc. ?d. ?

58. Methohexitone:a. has a molecular weight of 285 no, more like 257b. has a melting point of 158 degrees que??c. a 2.5% solution is isotonic ??d. is yellow whitee. has 4 isomers

59. Methohexitone:a. is an oxythiobarbiturate oxybarbb. breakdown is principally by splitting of ring no, 4 hydroxylationc. ?“longer duration than thio” shorterd. ?“greater protein binding than thio” less PBe. ?none of these

60. Benzodiazepine binding site on GABA receptor is:

a. near Cl channelb. inside the channelc. outside the channeld. on the alpha subunit some texts add the subunit

61. The drug with the largest volume of distribution at steady state is:a. propofol 3 – 10 litres/kgb. midazolam 1 – 1.5c. etomidate 2.5 – 4.5d. thiopentone 2.5e. methohexitone 2

62. GABA:a. is the principal inhibitory neurotransmitter in the spinal cord whole CNS – so this is part

of the truth ? glycine in the cord?b. barbiturates decrease the dissociation time between GABA and its receptor ie GABA

spends more time associatedc. ?? A and B types

63. Propofol is structurally related to:a. althesinb. etomidatec. ketamined. ?e. none of the above

64. Midazolam:a. water soluble at physiological pH nob. undergoes oxidative metabolism 1 and 4 hydroxylation on diazepine ringc. more lipophilic than lorazepam more lipid sol than diaz and lorazd. causes hypotension yes, CO and SVRe. has pKa of 7.4 (or ?8.1) 6.2f. causes retrograde amnesia no

65. Thiopentone:a. is the sulphur analogue of phenobarbitone pento, not phenob. has higher protein binding than its oxyanalogue yes – more lipophilic, as S not Oc. ?6% sodium bicarbonate 30 mg Na2CO3

d. isotonic at 2.5% concentration ???e. ?

66. Propofol clearance is significantly increased in:a. elderly Stoeltingb. metabolic acidosisc. pregnancy enzyme induction/inhibition variabled. ?e. ?can’t see that any of these is true

67. Thiopentone a. 100% reabsorbed in renal tubule almost 100%b. does not cross the placenta in significant amounts due to high plasma protein binding PB

75%c. ?? accumulates in the fetus [F] < [M]d. tachyphylaxis if multiple administration in short period Stoelting 122 – 123 describes

acute tolerance as developing quickly, mandating up to sixfold dose increases – so would d be better than a??? but more recent studies have shown tachyphylaxis does NOT occur

68. Ketamine:a. direct acting negative isotopeb. ?indirectly acts on sympathetic nervous system peripherally central effectc. directly on the sympathetic ganglia nod. is a competitive antagonist at NMDA receptors non-competitivee. directly stimulates alpha and beta receptors

69. With regard to GABA receptors, (which of the following is INCORRECT):a. GABA-A is found all over the body nob. Is an excitatory transmitter in 20% of CNS synapsesc. GABA-B is predominantly post-synaptic bothd. GABA receptor located in spinal cord, medulla and cortex yes, plus hypothalamus,

cerebellum, midbrain and hippocampuse. Is metabolised by deaminationf. Is metabolised by transamination GABA is (2 steps to succinate)g. Stimulated by benzodiazepinesh. Opposes action of glycine(Above is a composite of options from two questions in July 2001 paper.)

70. Propofol:a. Causes decreased hepatic blood flow to influence its own clearance Miller 250 says may

causeb. Relatively low clearance in children no - > (Miller 250)c. Has a high rate of transfer from the peripheral to the central compartment on ceasing an

infusion d. Has clinically significant metabolites inactivee. Elimination half-life of 5 minutes 4 – 23 hrs

71. Which one of the following induction agents does NOT exert its main effect via the GABA receptor?a. ketamineb. thiopentonec. propofold. midazolame. methohexitone

Local Anaesthetics MCQs

72. Lignocaine has a pKa of 7.9, at pH 6.9 the percentage ionised is:a. 1%b. 10%c. 50%d. 90%e. 99%

73. Cocaine:a. blocks reuptake of dopamine and noradrenaline Katzung 537b. central effects are due to noradrenalinec. crosses lipid soluble membranes because its pKa is 2.8 ??pKad. is not metabolised by plasma pseudocholinesterasee. rapidly absorbed by nasal mucosa

74. Ropivacaine: ??? a. produces greater motor block than bupivacaine Miller 502, 515 – no diff / studies

conflict; Stoelting 175 same B=R altho’ prevaricates somewhat; if the option were R<B and the other options were as recalled I’d go for it, but I wouldn’t go for R>B

b. is prepared as the R enantiomer Sc. is less lipid soluble than lignocaine >d. has the same cardiotoxicity as lignocaine ropiv more cardiotoxic than lig – Stoelt 171

75. Ropivacaine: ?????a. is a pure R isomer sb. is an isomer of bupivacaine crapc. provides more motor block than bupivacaine nod. has more toxicity than bupivacaine <e. has similar physico-chemical properties to bupivacaine not really – it’s a single

enantiomer and is 8 times less lipid soluble than B; on the other hand they have the same pKa

76. Ropivacaine differs from bupivacaine mainly by:a. more motor blockade than bupivacaineb. mainly affecting A beta rather than A delta fibresc. lower cardiac toxicity than bupivacained. ?e. none of the above

77. Bupivacaine:a. is an aminoester local anaestheticb. is formed by substituting butyl for methyl on amino group of mepivacaine Stoelting 175c. ?less/more toxic than tetracaine T > Bd. adrenaline solution contains sodium metabisulphite Marcain™ with adrenaline contains

sodium metabisulfite (product info)e. equipotent to etidocaine in causing motor block B < E (Miller 503)

which suggests we shouldn’t refer to the N in the piperidine nucleus as an amino N. Of course, logic by exclusion is dangerous here.

78. With regard to molecular weight of local anaesthetics, which is the correct sequence?a. cinchocaine>bupivacaine>lignocaine>prilocaine on the basis of counting C atoms!b. bupivacaine>lignocaine>cinchocaine>prilocainec. bupivacaine>lignocaine>prilocaine>cinchocained. prilocaine>bupivacaine>cinchocaine>lignocainee. lignocaine>bupivacaine>prilocaine>cinchocaine

79. Lignocaine works by:a. altering Na permeabilityb. altering membrane structurec. reduced Ca permeabilityd. increased K permeabilitye. Ca binding to tropomyosin

80. Lignocaine:a. has active metabolites some are anti-arrhythmic (Peck 133)b. metabolism faster in females because of progesterone yes induction but high HER so

little differencec. metabolism is independent of liver blood flow high HER, so nod. ?

81. Protein binding of local anaesthetics (in decreasing order):a. procaine>bupivacaine>lignocaine>prilocaineb. bupivacaine>lignocaine>prilocaine>procainec. prilocaine>bupivacaine>lignocaine>procained. lignocaine>bupivacaine>prilocaine>procainee. bupivacaine>lignocaine>procaine>prilocainef. bupivacaine>procaine>lignocaine>prilocaineB 95 L 70 Pril 55 Proc 6 (Peck 132)

82. Local anaesthetics are metabolised in the following order:a. bupivacaine>ropivacaine>lignocaine>prilocaine>procaineb. above in different orders.

Elim half life Proc short, lig/pril 100’, mepiv 115’, ropiv 120’, bupiv 160’ (Peck 132)

83. Saxitoxin site on sodium channel is:a. inside channelb outside channelc on membrane outsided ?

Rang & Dale Pg 643: "...unlike conventional local anaesthetics, act exclusively from the outside of the membrane..."

84. The site of action of benzocaine is: there is truth in b and ca. same site as saxitoxinb. inside Na channel c. at axoplasmic end of Na channeld. at Ca channele. in the cell membrane

85. What factor does not influence the peak plasma levels after epidural injection of local anaesthetic?a. vasoconstrictorb. natural vasoconstrictor activity of the drugc. hepatic clearanced. renal clearance

86. Which ONE of the following is an amide?Miller 492, Stoelt 159a. tetracaineb. procainamidec. procained. prilocainee. cinchocaine

87. The following are all amides except:a. bupivacaineb. prilocainec. etidocained. tetracainee. dibucaine

88. A solution of local anaesthetic contains 1:100,000 adrenaline. How much adrenaline has been added?a. 0.01%b. 0.1%c. 10mcg/mld. 100mcg/mle. 1000mcg/mlf.

89. Regarding the addition of adrenaline to a local anaesthetic administered epidurally, which of the following is NOT true?a. significantly prolongs the duration of action of bupivacaine nob. causes tissue acidosis at the site of injection true – in Cousins (a) because

vasoconstriction and (b) because low pHc. causes vasoconstriction yes

90. Regarding local anaesthetic plasma protein bindinga. is predominantly by albuminb. is predominantly by alpha-1-acid glycoproteinc. is greater for tetracaine than for bupivacained. neonates have a greater number of binding sitese. plasma binding is directly proportional to local anaesthetic concentration

91. For a local anaesthetic agent at a given concentration:a. effect is NOT dependent on resting membrane potentialb. faster onset with increasing frequency of stimulation of nerve M 500c. unionised form blocks the surface receptord. agent blocks the channel in the activated state both M 499e. faster onset with more negative resting membrane potential

Muscle Relaxants & Antagonists MCQs

92. With regard to tetanic stimulation by a nerve stimulator:a. used to determine residual curarisation can be – but a tad obsoleteb. degree of fade is independent of stimulus duration wrong M 353c. degree of fade is dependent on stimulus intensity not if supramaxd. used to check depth of anaesthesia !!!!!!!!

93. Hyperkalaemia with suxamethonium is associated with: I’d go for e over aa. abdominal infection M 423 – esp if > 1/52b. Parkinson’s disease no - M 970c. Meningomyeolocoeled. Cerebral palsy M 2139e. Myotonic dystrophy M 973

94. Which of the following is NOT metabolised by plasma cholinesterase?a. procaineb. Cocainec. dibucaine amided. suxamethoniume. Esmolol rbc estersf. mivacurium

95. Which of the following is metabolised by plasma cholinesterase?a. Remifentanil nonspecificb. Procaine BuChEc. Esmolol rbcd. ?e. all of the above

96. Esterases metabolise all EXCEPT:a. remifentanilb. dibucainec. pyridostigmine 75% excr unchanged but does contain an ester bondd. ?

97. The action of nondepolarising neuromuscular blocking agents is PROLONGED by:a. respiratory acidosis yes - M 468b. increased temperature no – M 462c. increased calcium no – M 463d. increased potassium no – M 469 prolongse. decreased magnesium no – M 462 Mg prolongs

98. Agents prolonging nondepolarising NMBDs by desensitising the post-junctional membrane:a. phenytoin no – M 464 accelerates recoveryb. halothane no – M 462 – mooted onlyc. lignocaine yes – M 464d. verapamil no – M 464

99. Which drugs (?competitively) inhibit acetylcholinesterase?a. neostigmineb. pyridostigminec. physostigmined. edrophonium competitive – rest are covalent so noncompetitivee. all of the above

100. The activity of plasma cholinesterase is decreased by the following drugs except:a. neostigmineb. organophosphatesc. THA tetrahydroaminoacridine – Katzung 1040d. Maxalon M 420e. Cimetidine no – M 420

101. Regarding vecuronium:a. it accumulates in renal failure its metabolite 3 desvec does, prolonging effect, but vec

itself does notb. is a benzylisoquinolinium steroidc. is a bisquaternary amine monod. is more lipid soluble than pancuronium as vec is monoquaternary and panc is

bisquaternarye. is predominantly renally excreted hep

102. In reversing neuromuscular blockade, which of the following combinations is best matched with respect to time of onset?a. Atropine and neostigmineb. Atropine and glycopyrrolatec. Atropine and edrophoniumd. Glycopyrrolate and edrophoniume. Atropine and physostigmine

103. Plasma cholinesterase:a. metabolises dibucaineb. metabolises Esmololc. hydrolyses Mivacurium at 80% the rate of suxamethonium M 452d. is unaffected by neostigmine

104. Suxamethonium:a. bigger molecule than vecuroniumb. needs to occupy 80% of nicotinic receptors to get effectc. resistance to hydrolysis by acetylcholinesterased. ?is an antagonist at nicotinic receptorse. increasing dose produces similar block

105. With regard to the nerve stimulator in competitive blockade:a. fade is dependent on stimulating frequency M 1353b. TOFC of four is a sign of adequate reversal can still have some fade with count of 4c. ?d. ?

106. Anticholinesterase agents:a. carbamates duration of action is related to the time required for dissociation from the

anionic site esteratic Peck 155b. carbamates act by acetylation of the esteratic site carbamylationc. ?Comment (PD): Both of these are incorrect.

107. Carbamylation of acetylcholinesterase:a. ionic bonding at anionic siteb. ionic bonding at esteratic sitec. covalent bonding at anionic sited. covalent bonding at esteratic sitee. none of the above

108. Mivacurium:a. is metabolised at 80% the rate of suxamethonium M 452, St 217b. takes 15 minutes from ED95 dose to recovery of 95% twitch heightc. has an ED95 of 1.5mg/kg 80g/kg St 216d. trigger for malignant hyperthermia noe. duration of action is increased in renal failure yes – M 453

109. Mivacurium:a. twice the ED95 dose is 1.5mg/kg 0.15 mg/kgb. is metabolised at 80-90% the rate of suxamethonium yepc. after 2 x ED95 dose 95% return of twitch height after 15 mins no – St 184 table has 25%

after 12 – 20 mind. does not usually require reversal practically true, but in an exam?e. duration of action may be prolonged by anticholinesterases yes

110. Mivacurium administered at a dose of 2 time the ED95 dose produces relaxation for:a. 10 minsb. 15 minsc. 20 mins no ref for this – looks about right from graph on M 453d. 25 minse. none of the above

111. The recovery index 25 to 75% is 7 minutes for which drug?a. vecuroniumb. rocuroniumc. Mivacuriumd. Suxamethonium

Http://www.anaesthetist.com/anaes/drugs/ndmr.htm Table gives sux recovery index as 5 minutes, miva as 30-35 min...

112. A muscle relaxant is administered at twice ED95 for a short dental case. Return of normal TOF ratio occurred at 7 minutes. The muscle relaxant used was:a. Suxamethonium ie we all check TOF after sux and b4 nondepolariser, don’t we?b. vecuroniumc. atracuriumd. rocuroniume. Mivacurium

113. Release of acetylcholine at motor endplate:a. ??gentamicin Stoelt 473 says both ACh release and stabilise Postjunctional membraneb. botulinum toxin works by??c. ?d. ?Comment (PD): Botulinum works by inhibition of synthesis or release of ACh.

114. Release of acetylcholine at motor endplate:a. hemicholium directly interferes with release blocks Ch uptake / slows ACh synth –

Katzung 89

b. only in response to action potential wrong because prejunctional nicotinic receptorsc. decreased by aminoglycosides by a prejunctional effect yes per Stoeltd. is a Ca dependent process yes M 738 – best option as C is still a bit speculativee. always causes an action potential noComment (PD): Hemicholinium is a synthetic compound which blocks the transport system by which choline accumulates in the terminals of cholinergic fibres, thus limiting the synthesis of ACh store available for release.)

115. Gentamicin potentiates non-depolarising neuromuscular block by:a. interfering with Ca influx for exocytosis I don’t think the detail is inb. ?c. ?

116. Rocuronium:a. monoquaternary at physiological pH St 213f. more lipid soluble than pancuronium roc is monoquaternary and panc is bisquaternaryb. 30% metabolised (?deacetylated) in the liver mostly excreted unchanged in bile with up

to 30% renallyc. rapid onset is due to its high potency low potencyd. fastest onset is with 2 times ED 95 dose 3 x ED 95 (M 449)e. is bisquaternary

117. Plasma cholinesterase is inhibited 80% by 10-5 molar dibucaine:a. in late pregnancy no – normal quality, quantityb. ?c. ?

118. Which of the following do NOT prolong neuromuscular blockade?a. volatile anaestheticsb. antibioticsc. phenytoin shortens (M 464) as does carbamazepine – reason thought to be kinetic not

dynamic; details not clear (phenytoin as dual action. Also see examiners report for 1997 Aug/Sept Question 11. )

d. beta-blockers except perhaps propranolol??? Not listed in S or Me. hyperthermia no effect M 462

119. Malignant hyperthermia causes:a. hypertensionb. whole body rigidityc. tachyphylaxis with a suxamethonium infusion Well, yeah – rigidity is the opposite of the

relaxant effect desired when sux is given…d. ?

120. Edrophonium:a. longer half-life than neostigmine Edroph elim t1/2 110min cf neostig 15-80min

(Smith&Sesada)b. onset slower than neostigminec. ?pyridostigmined. binds to anionic site of cholinesterasee. relieve symptoms of myasthenia gravis hence tensilon testf. ?is reliable in reversing a phase II block not reliably

121. Atracurium:a. has an active metaboliteb. ester metabolism is a minor pathway of eliminationc. metabolism is by Hofmann elimination which is pH dependentd. ? for the racemate most metab is ester hydrolysis; then Hofmanne. ?

122. What muscle relaxant has an active metabolite with a half-life twice that of the parent compound?a. Rocuronium m 449b. vecuronium M 448 ?shorter half lifec. pancuronium M 447 3-OH panc has same half life as pancd. atracurium M451e. none of the above

123. Succinylcholine can cause:a. bradycardiab. histamine releasec. tachycardiad. hypertension via MHe. all of the above

124. Neostigmine reversal of nondepolarsing neuromuscular block:a. not affected by enflurane at 2 MAC is affected - M 468b. varies depending on use of NDMR by bolus or infusion I can’t find anything on thisc. is/isn’t affected by age Stoelt 229 – neo – less needed in littlies, thought to be a dynamic

not a kinetic effect; no diff for edro.d. ?

125. Which of the following is associated with a decrease in duration or effect of nondepolarising blocking drugs:

a. volatile anaesthetic alkanes prolongb. volatile anaesthetic ethers prolongc. aminoglycoside antibiotics prolongd. aminopyridine derivatives reverse – K channel antag – prolonged depolarisation and

ACh releasee. local anaesthetic esters prolong

126. Which of the following decreases the duration/depth of neuromuscular blockade?a. enflurane at 2 MACb. aminoglycosidesc. bolus doses versus infusion why would it?? Ref??d. aminopyridines

127. Neuromuscular blockade NOT prolonged by:a. hyperthermiab. gentamicinc. volatile agentsd. hypothermiae. ?

128. Neostigmine’s mechanism of action:a. binds covalently to esteratic site on AChEb. binds electrostatically to esteratic site on AChEc. binds to anionic site forms H bond at anionic sited. forms complex with AChE with a shorter half-life than acetylcholine far longere. ?

129. With depolarising neuromuscular blocker:a. is competitively antagonised by NDMR no specific reference for this; it probably is

displaced by NDMRb. “something about tetany and fade” neither occursc. ?d. ?e. shows post-tetanic potentiation no – Peck 139

130. Rocuronium administered in 2 times the ED95 dose:a. rapid onset, short durationb. rapid onset, intermediate durationc. slow onset, intermediate duration usu give 3 x ED95

d. slow onset, long duratione. “some other combination”

131. Anticholinesterase drugs:a. ?b. ?c. Used in treatment of Glaucoma echothiopated. ?

132. Neostigmine:a. tertiary ammonium compound quaternaryb. ?c. ?

133. The dibucaine number for a normal person is:a. 20b. 40c. 60d. 80e. 100

134. Muscle relaxants are less likely to cause anaphylaxis if:a. injected slowly this applies to histamine release (eg atrac) rather than anaphylaxisb. suxamethonium is the most common cause debatable – alcuronium, rapacuroniumc. H1 and H2 blockers prevent anaphylaxisd. Always fatale. ?

Opioids

135. With regards to pethidine’s physical properties:a. it has an octanol coefficient of 10 39 per Miller 312b. it has a pKa of 8.4c. ?d. ?e. ?

136. Which factor does NOT predispose to bradycardia with fentanyl in doses of 50mcg/kg?a. Calcium channel antagonist Miller 299b. Beta-blocker Miller 299c. Benzodiazepines ?ref but yesd. ?e. Slow injection of drug

137. Naloxone:a. is not an antagonist of agonist-antagonist drugs probably is - ?refb. is not an antagonist at ?mu and sigma receptorsc. causes pulmonary oedema Peck 112 d. can cause hypotension in experimental shock animal models opposite – Miller 349e. may cause an abrupt increase in sympathetic tone Peck 112, Stoelt 107

138. Diagram of numbered structure of morphine. Which substitutions are correct? Miller 278; 14-OH gives antagonista. N-17 substitution gives antagonist activity mixed ag/antag (best of these)b. C6 methylation produces codeine C3c. Glucuronidation occurs at C2 C3, C6d. Diacetylation decreases lipid solubility increases (diamorph) Peck 105

139. Also:a. C3 and C6 increase lipid solubility acetylation at these increases lipid solubilityb. Acetyl group on ?C3 gives heroin C3, C6c. N-substitution gives antagonist mixed ag/antagd. C5 glucuronidation site C3, C6e. C3 methyl gives codeine

140. Pethidine in doses of 2 to 2.5mg/kg causes all of the following EXCEPT:a. bradycardiab. decreased systemic vascular resistancec. decreased BPd. increased cardiac output –ve inotropy in large doses Stoelt 92

141. Regarding the clearance of morphine:a. affected by cirrhosisb. affected by hepatic blood flowc. shows low hepatic extraction ratio high HER 14 ml/kg/mind. ?e. ?

142. Fentanyl:a. with pKa 8.4 is 90% ionised at physiological pHb. has an octanol coefficient of 10 600 - 900c. is 1,000 times more potent than morphine 100 xd. has first-pass lung uptake reduced to 20% by propranolol ‘substantially reduced’

clearance of fent per Stoelt 293 – so 2 – 4 x as much fent enters circulatione. has up to 50% uptake in the lung >50%, saturablef. elimination half-life < 2 hoursg. carried on albumin mostlyh. carried on alpha-1 acid glycoprotein mostly as basici. can cause hypertension with MAOi

143. An opioid which can not be used for TIVA:a. morphine

b. pethidine because of norpeth, but you wouldn’t go for fent or morph eitherc. fentanyld. sufentanile. alfentanil

144. Nalbuphine: neither answera. works at mu receptor only antagonist, agonistb. has same side effects as pentazocine pent releases catecholamines – not nalbuphc. ?d. ?

145. Pethidine:a. 100mg is equal to 10mg morphine in effect Stoelt 91b. increases heart ratec. no effect on cardiac output –ve inotrope in large dosesd. is preferred to morphine for analgesiae. ?

146. Pethidine produces:a. miosis Stoelt 93 says it causes mydriasis, whereas Peck 108 says miosis, but not as much

as morph: b. more severe hypotension with comparable doses of morphine more reduction in SVR; -ve

inotropy at high dose; orthostatic hypotension as interferes with SNS mediated reflexes more than morph

c. more biliary spasm than morphine lessd. ?

147. TIVA with morphine causes the following EXCEPT:a. mydriasisb. muscle rigidityc. respiratory depressiond. ?

148. Codeine: all wronga. substitution at C6 position of morphine C3b. 10% of codeine is metabolised to diacetyl morphine morphinec. IM 100mg is equivalent to 10mg morphine IM ½ potency M 343 p102 Stoelt, 120mg

Codeine IM equivalent to 10mg Morphd. Methyl substitution at C5 position of morphine C3e. Can be safely given IV because causes no histamine release no, causes BP M 344f. Has higher first pass effect than morphine C: 50% M: 75% Peck 106

149. Morphine metabolism:a. principally metabolised to morphine-6-glucuronide M3Gb. metabolites have shorter half-life M6G = M, or greater (Stoelt 84)c. found in extrahepatic sites renal up to 40% Miller 313d. metabolites freely cross the blood-brain barrier yes, as M6G is activee. all have analgesic effect no, normorph and M3G don’tf. are 30% renally excreted 90%g. in neonates, predominantly by sulphationh. in adults, mostly to morphine-3-glucuronide 75 – 85% M3G, 5 – 10% M6G, 5%

normorph and a small amt of codeine! Stoelt 84

150. Sufentanil: Miller 312, 315; Stoelt 96 - 98a. 30 times as potent as fentanyl 10 xb. <7% excreted unchanged in urine Less than 1% - Stoelt 97c. greater protein binding than fentanyl S 93%, F 80% S and M agree (hmmm – S and M –

hadn’t noticed that before)d. half-life of elimination between fentanyl and alfentanil F 3 – 6, S 2 – 4, A 1.5 per Stoelt

83; Miller has S and F overlapping moree. predominantly bound by ?albumin/?alpha-1 acid glycoprotein

151. Pethidine is the traditionally favoured opioid in obstetrics because:a. norpethidine does not cross the placentab. does not undergo ion trappingc. causes less neonatal depression Miller 308; Stoelt p90 for Cd. it does not cross the placenta e. it is thought to cause less respiratory depression in the neonate

I wonder if C and E are 2 slightly diff recollections of the same option and a fifth option was not recalled. Otherwise… sad babies? They do cry a lot (personal experience x 3!)

152. Alfentanil is more lipid soluble than fentanyl because: a. has a pKa of 8.4 and is 90% unionised at physiological pHb. ?’N-octanal coefficient is [some five digit number]”c. ?d. ?pKa is 6.5 so 90% un-ionised at 7.4; octanol coefficient is 145

153. Alfentanil works faster than fentanyl because:a. more lipid solubleb. higher concentration unionised at physiological pH c. ?d. ?e. ?

154. Tramadol: + enantiomer blocks 5HT reuptake, - enantiomer blocks NA reuptake, M1 is a agonist. Clinical effects are 40% agonism, 40% NA reuptake and 20% 5HT reuptake – analgesic synergy (Stefan Schug lecture at ASA 2002)

a. has beta-blocking propertiesb. blocks noradrenaline reuptakec. has greater opioid activity than morphine <d. is directly inhibited by yohimbinee. only the +ve enantiomer is active

155. The most unlikely thing to occur with morphine administered in recovery is:a. constipationb. respiratory depressionc. sedationd. nausea and vomitinge. physical dependence takes 48 hrs to develop; fully developed by 3/52f. pruritus

156. Extrahepatic de-esterification of remifentanila. occurs in RBCs Miller 316b. by plasma cholinesterase non-specific esterases; ‘plasma esterase’ = BuChEc. NOT in incubated blood ?? apparently there was a reference to this in a recent episode of

Buffy (which I have never watched but which is now the subject of some tertiary courses!!)

d. Has clearance less than 1l/min 30 – 40 ml/kg/min so > 2 l/min (miller 312)e. Has an active metabolite no – Miller 316f. Hydrolysis does not occur in vitro in incubated bloodg. The drug is hydrolysed to an active metabolite which undergoes further hydrolysis ??

157. The following are metabolites of morphine except:a. morphine-6-glucuronideb. morphine-3-glucuronidec. normorphined. codeinee. hydromorphone 75 – 85% M3G, 5 – 10% M6G, 5% normorph and a small amt of

codeine! Stoelt 84

158. Fentanyl given at dose of 50-150mcg/kg:a. causes potent cardiac depressionb. does not cause muscle rigidityc. has an elimination half-time of more than 3 hours F 3 – 6 per Stoelt 83d. not enough to relieve the stress response to surgerye. preserve cardiac output

Anticholinergics/Antimuscarinics

159. Glycopyrrolate:a. has mandelic acid rather than tropic acidb. tertiary amine quaternaryc. ?d. ?

160. Hyoscine:a. ?b. quaternary ammonium compound tertiaryc. ? d. causes mydriasis yes, scop > A > G Stoelt 244e. causes confusion in the elderly yesComment (PD): Also causes D, but has more potent CNS effects.If I had to choose I would go for D, because it is consistent whereas E is variable

161. Scopolamine d & l isomers:a. d is active L is active Stoelt 238;scopolamine is L-hyoscinec. provided as racemic productd. doesn’t cause central effectse. ?

162. Atropine:a. ?b. increases anatomical and alveolar dead space bronchodilatorc. ? I can see how it causes Inc Anat DS but how does it inc Alv DS??d. ?

163. Atropine and glycopyrrolate:a. both are naturally occurring G syntheticb. ? cause confusion in the elderly G does not cross BBB.c.d. ??

Psychotherapeutic Drugs

164. Benzodiazepines:a. all are lipid soluble (OR: None are water soluble)b. are all renally excreted unchanged crapc. causes retrograde amnesia nod. lorazepam is more lipophilic than diazepam less – Stoelt 136, Miller 230e. block GABA receptors nof. have high therapeutic index yesComment (PD): A is correct at physiological pH.

165. Which is TRUE regarding monoamine oxidase inhibitors (MAOi)?a. should/must be ceased for two weeks prior to general anaesthesia no, may dangerously

worsen depression (Peck 248)b. cause hypotension and sedation in combination with pethidine BPc. inhibit activity of indirect sympathomimetics inhibit their metabolism by MAO, leading

to hypertensive crisisd. ingested tyramine causes hypertension due to indirect effects I guess they are indirecte. includes doxepin and amitriptyline these are TCAs

166. Neuroleptic malignant syndrome: which is best??a. occurs only with chronic use falseb. 80% (60%) mortality 20 – 30% Katzung 488c. treated with dantrolene katzung 489d. can be caused by acute withdrawal of L-Dopa therapy Yentis 382e. Is treated with bromocriptine katzung 489

167. Benzodiazepines: Miller 236a. have no analgesic effectb. have an antanalgesic effectc. have an analgesic effectd. have dose-related analgesic and antanalgesic effects

168. The benzodiazepine with the longest elimination half-life is:a. diazepam 20 – 80 katzung 368b. oxazepam 10 – 20 katzung 368c. temazepam 10 – 40 katzung 368d. midazolam 1 – 4 Peck 243e. lorazepam 10 – 20 katzung 368f. flunitrazepam 20ish K Llewellyn personal communication (unpublished)

169. Fluoxetine:a. inhibits noradrenaline and adrenaline uptakeb. inhibits serotonin uptake SSRIc. ?d. ?

170. Flumazenil: Stoelt 138, Miller 237 - 9a. formulated in propylene glycol in commercial preparation Aqueous solution (product

info)b. inverse agonist weak agonistc. is slowly metabolised making resedation unlikely no no nod. does not reliably reverse sedation and respiratory depression high affinity, so surely

false… then again depends on cause of sedatione. is a partial agonist at mu opioid receptors no ref for this

171. Diazepam:a. half-life of 5 to 10 hoursb. metabolised to oxazepam and desmethyldiazepamc. ?d. ?

172. Droperidol:a. substituted phenothiazine Butyrophenones are phenothioazine derivatives but its structure

is quite different so I think to call it substituted is drawing a long bowb. reliably produces mental tranquillity no, may mask fear – Stoelt 373c. does not act (directly) on CTZ Stoelt 375d. alpha-blockade with hypotension is not a problem with 2mg dose the drop in BP is mild

Stoelt 374e. slows alpha rhythm on EEG rhythm persists Stoelt 373 – 4 but is slowed Miller 257 so

perhaps this is the best answerDebate as to whether D or E is a better answerIf the drop in BP is only mild doesn’t that make it “Not a problem” and thus D would be true Hear hear

173. Monoamine oxidase inhibitors: Stoelt 366a. moclobemide is a reversible inhibitor only of MAOIA

b. interacts with tyramine to cause hypertensionc. interacts with pethidine to cause hypothermia hypertension

They don’t interact with Tyramine, They prevent interaction with tyramine.I think A is the best answer

174. Metabolites of diazepam, all EXCEPT:a. temazepam b. oxazepamc. desmethyldiazepamd. lorazepam

175. With respect to action of midazolam: none is correcta. acts on GABA-B receptors Ab. increases duration of opening of Cl- channels freqc. ?competes with barbiturates for receptor site on GABA receptor different sites: BDZ on

or subunit; barbs on subunitd. metabolism is decreased by cimetidine H2 antags don’t affect midaz metabolism

(whereas they do affect diazepam (oxidative microsomal metab) but not lorazepam (glucuronidation)…) Stoelt 129

e. decreases chloride conductance f. interacts with B1 subunit of GABA or subunit

176. Tricyclic antidepressants:a. do not cause sedation dob. formed from modification of the phenothiazine ring katzung 499c. avoid anti-cholinergic effects compared to other anti-depressants crapd. does not decrease reuptake of serotonin do – interfere with reuptake of 5HT and NA

Stoelt 360e. decrease CNS amine levels

177. Diazepam 0.1mg/kg given orally, the percent absorption is:a. 100%b. 94%c. ?d. ?e. we thought if q asks ‘absorption’ then 100% if ‘BA’ then 94%Comment (PD): Benzodiazepines are completely absorbed but the oral bioavailability of diazepam is 90%.

Cardiovascular Drugs

178. Milrinone:a. decreases pulmonary vascular resistance yesb. increases systemic vascular resistance c. is poorly absorbed when given orally available orally so unlikelyd. chronic use causes thrombocytopenia may cause thrombocytopenia Katzung 209; but not

used chronically as increases cardiac mortality

179. Milrinone:a. chronic use causes thrombocytopeniab. pulmonary vasoconstrictionc. not effective orallyd. ?e. ?

180. Milrinone:a. cannot be given orallyb. is a phosphodiesterase III inhibitor that decreases cAMP c. decreases peripheral vascular resistanced. increases pulmonary vascular resistance

181. Milrinone:a. is structurally related to thyroid hormone bipyridineb. is arrhythmogenic no, per Stoelt – yet arrhythmia is its mechanism of increased mortality

with long term oral use.c. has its effects via cAMP mediated increase in intracellular Ca definitelyd. increases myocardial oxygen consumption minimal increase Stoelt 284

182. Sodium nitrite used in cyanide toxicity:a. increases methaemoglobinaemiab. to produce increased hepatic sulphydryl groups Na thiosulfate donates sulfur to convert

cyanate to thiocyanatec. increases conversion to cyanocobalamin B12 does thisd. displaces cyanide from haemoglobin high FIO2

e. enhances oxidative phosphorylation no

183. Ephedrine:a. is resistant to metabolism by MAO slight MAO susceptibilityb. is metabolised by COMT noc. action is totally indirect no – direct and indirectd. acts via direct and indirect beta effect and - Stoelt 270e. action is purely alpha agonist no

184. Ephedrine:a. has direct alpha actions onlyb. has direct beta actions onlyc. has indirect alpha actions onlyd. ?e. has both indirect and direct actions on alpha and beta receptors

185. Ephedrine:a. increases skeletal muscle blood flowb. acts only by indirect effectsc. not metabolised by GIT MAOd. not metabolised COMTe. increases renal blood flow

186. Ephedrine has:a. direct agonist on alpha receptorsb. direct and indirect effects on alpha and beta receptorsc. indirect actions on alpha receptorsd. direct actions on beta receptorse. indirect actions on beta receptors

;187. The principle (?urinary) metabolite of adrenaline is:a. normetanephrine this is the chief urinary metabolite of NAb. metanephrinec. 3,4 dihydroxymandelic acidd. 3-methoxy-4-hydroxymandelic acid Stoelt 264 ie VMAe. 3-methoxy-4-hydroxyphenylalanine

188. Thiazide diuretics:a. work mainly on PCT DT, though oddly Stoelt alone suggests a minor effect on PCT 435b. not effective if severely sodium depleted ? ref for this – makes some sensec. action is independent of acid-base balance Stoelt 435d. increase GFR immediately may GFR peck 272e. decrease BP by decreasing contractility no direct cardiac effectf. cause hypoglycaemia hyperglycaemia Stoelt 436g. interferes with kidney concentrating mechanisms if PCT effect then yes - ?refh. causes hypocalcaemia enhance Ca reabsorption Katzung 255i. used to treat hypercalcaemiaj. potentiate hyperglycaemiak. are effective as antihypertensives by decreasing cardiac output no direct cardiac effect

189. Thiazide diuretics:a. increase calcium excretion in the urineb. decrease efficacy in sodium depletion ????????c. main site of action is the proximal tubulecause equivalent amount of diuresis to frusemide I always thought that loop diuretics were potentially more potent as more of the filtered load reaches them, but Stoelt (table 25 – 3, p 437)says max diuretic effect of loop diuretics 8 ml/min and thiazides 13 ml/min ‘High ceiling diuretic’ is an old term for loop diuretic which would reinforce the view that frusemide ought to be stronger

190. Sodium nitroprusside in healthy patient:a. decrease venous more than arterial resistance GTN does this – nitroprusside is equal

product info states venodilation>arterial although everywhere else says equal!b. has no effect on control of pulmonary vascular resistance HPV Stoelt 319c. decreases cerebral blood flow CBFd. causes uterine relaxation Stoelt 315 says lacks FX on nonvasc smooth musclee. does not inhibit hypoxic pulmonary vasoconstriction does so

191. Which one of the following statements about clonidine is correct?a. increase MAC requirements b. cause transient hypertension with IV administration yes but C is more completec. with IV bolus causes hyper- then hypotension

d. causes hypotension immediately noe. is not administered transdermally is available transdermally

192. Regarding digoxin:a. the aglycone portion causes the cardiac effects Stoelting has a lovely helpful typo on p

278, directly contradicting himself in consecutive sentences. My old copy of Rang and Dale confirms that it’s the Aglycone part that is active; the glycone binds it to the heart

b. the glycone portion causes the cardiac effectsc. ?d. ?

193. Which of the following ECG changes would be most likely in digoxin toxicity: Stoelt 279, Katzung 207a. Increased PR interval Stoelt 281; K 207 – occurs before arrhythmia, although this change

is evident at therapeutic levels so that makes a case for E; however Stoelt emphasises PR lengthening in the toxicity bit

b. Increased QT interval shortenc. Peaked T waves invertedd. ST elevation depression/scoopinge. Ventricular extrasystoles yes because of increased automaticity

194. Digoxin toxicity:a. inverted T waves therapeuticb. prolonged PR intervalc. xanthopsia oddly not mentioned by Stoelt – hasn’t he heard of Vincent Van Gogh?d. prolonged PT interval shortened

195. Regarding digoxin overdose/toxicity:a. serum level >2.1ng/ml is toxic I’d have thought so but Stoelt 282 says > 3 ng/mlb. yellow vision I’m still amazed – I dined out for years on the Vincent – yellow painting

theory You haven’t highlighted Xanthopsia or yellow vision. I thought that they were true (Bris course notes, Ian Cooper)

c. causes a long PR intervald. causes xanthopsiae. causes a long QT interval and bigeminy

196. Clonidine: - Peck 235 - 6a. elimination half-life of 3 hours 9 – 18 hrs b. excreted 50% unchanged in the urine Yes c. oral bioavailability 50% almost 100%d. cannot be absorbed topically can soe. is highly protein bound 20%

197. Adenosine: Peck 200 - 1a. slows conduction velocity and increases refractory period RP; does slow conduction

velocity at SAN and AVNb. is metabolised in plasma deaminated in RBC and endotheliumc. decreased urate levels as it’s a purined. methylxanthines increase response antagonise Stoelt 342Comment (PD): Adenosine shortens action potential duration and hyperpolarizes cardiac cell membranes and decreases the diastolic depolarisation (phase 4) of the pacemaker cells of the sinoatrial node.Absorbed from plasma into RBC and there phosphorylated and deaminated. (Sasada and Smith)

A causes AV block. Doesn’t that slow conduction velocity??

198. Catecholamine substitution:a. alpha carbon CH3 substitution gives beta selectivity methyl gives selectivity; alkyl

gives selectivityb. beta-hydroxy substitution gives increased affinity direct affinityc. D-dobutamine antagonist, L-dobutamine agonist no ref for thisd. ?

199. Esmolol:a. active at beta-1 and beta-2 receptors 2 at high doseb. half-life<2 minutes 9 minc. has methanol as metabolited. is metabolised by plasma cholinesterase rbc esterasee. is excreted unchanged in the urine <1% unchangedf. is a non-selective beta-1 receptor antagonist yeah right

200. Osmotic diuretics:a. less sodium delivered to distal tubule more Na but even more water, so osmolality is

lowerb. hypotonic medulla still hypertonic but < 1400 ? exact valuec. increased sodium lossd. urine osmolality>plasma osmolality <e. increased sodium reabsorption lessf. MW greater than 600 mannitol - 6 carbon opened out sugar – 182; urea teensy weensyg. Washes out the medullary interstitial gradient several reference state mannitol “washes

out interstitial medullary gradient” (eg smith and sesada, G&Gp695)

201. Osmotic diuretics:a. include mannitol and the dextrans dextrans are plasma expanders – 200 000 glucose units

strung together like a great big tangly line of undies coming out of the washing machine – not filtered by glomerulus

b. washout the medullary osmotic gradient several reference state mannitol “washes out interstitial medullary gradient” (eg smith and sesada, G&Gp695)

c. cause sodium retentiond. ?e. have a molecular weight >600

202. Guanethidine: Peck 232a. causes sedation as a side-effect doesn’t cross BBBb. postural hypotension occursc. decreases reuptake of catecholamines presynaptically displaces them from vesiclesd. ?

203. Guanethidine:a. acts primarily at the CNS doesn’t cross BBBb. produces anti-hypertensive effect primarily by presynaptically inhibiting release of

noradrenalinec. highly lipid soluble quaternary amined. mental depression is a troublesome side effect doesn’t cross BBBe. orthostatic hypotension is not a prominent side effect is

204. Labetalol:a. alpha agonist & beta agonist nob. alpha agonist & beta antagonist no c. alpha antagonist & beta antagonist yesd. is more potent alpha blocker than phenoxybenzamine < per Katzung 148; ¼ - 1/3 per

Stoelt e. alpha>beta effect Stoelt 300 - : is 3:1 orally and 7:1 IV

205. Frusemide: Peck 274 Stoelt 438a. 30% plasma binding 95% b. ??% absorption F = 65%c. elimination half-life less than one hour yep Stoelt 438d. promotes active secretion does not (Stoelt 438)e. affects the uricosuric effect of probenecid may cause hyperuricaemia (Stoelt 439)f. effects not decreased until large decrease in GFR ? refg. causes a diuresis with is dependent on GFR over a wide range Stoelt 437 - 8

206. Frusemide does not cause:a. hyponatraemiab. hypokalaemiac. hypouricaemiad. hypomagnesaemia yes, loss as lumen potential is less +ve (Katzung 253)e. hypocalcaemia Ca excretion up but plasma Ca not down

207. The anti-arrhythmic effect of lignocaine:a. because it increases the refractoriness of cardiac muscle reduced as phase 3 shortb. therapeutic level 2-5ng/ml Stoelt 332 says 1 – 5 g/ml so ng/ml is the wrong unitc. ?

208. The effects of beta-blockers – the following is not true. Katzung 145a. relax uterine muscle can’t find ref but I have my doubts – terbutaline and salbutamol are

tocolytics so if ventolin relaxes Ut.s.m, .. beta blockers unlikely to also relax…. Not trueb. increased AV conduction : Stoelt 296c. decreased lipolysis Stoelt 297d. increased SVR true,as effects of Adr unopposed Stoelt 296e. mask hypoglycaemia true Stoelt 296

209. Phentolamine: Stoelt 288a. is a selective alpha- antagonist nonselective b. binds covalently to the alpha receptor competitive / transientc. causes bradycardia tachy via baroreceptord. is a selective alpha-2 antagonist nonselectivee. increases cardiac output via baroreceptor plus loss of 2 presynaptic effectComment (PD): Not selective as also has some beta-adrenergic activity, some anti-serotonergic activity.

210. A non-selective beta-blocker with low extraction ratio, long half-life and ISA:a. atenolol selective, no ISAb. propranolol no ISA, high HERc. metoprolol selective, no ISAd. labetalol no ISA, high HERe. ?Comment (PD): None of these, atenolol and metoprolol are beta-1 selective, propranolol has a high hepatic extraction ratio as does labetalol.Answer is probably pindolol. Pindolol’s half life isn’t that long though

211. Which ONE of the following is water soluble, half-life 6-8 hours, (“and something else”)?a. Esmolol 10 minb. Metoprolol 3-4/24c. Propranolol 3-6/24d. ?e. atenolol 6-9/24

212. Sotalol:a. non-selective beta-blocker Stoelt 292, 341, TeOh 199b. contraindicated in long QTc. does ? to ?K current prolongs repolarisationd. used in the treatment of Torsades causes T de P in 0.5% of those on 80 mg od; 5.8% if

320 mg/d.e. class II anti-arrhythmic drug class II - III

213. Trimetaphan: Stoelt 326a. crosses the blood brain barrier quaternary ammoniumb. incompatible with thiopentone B correct (Smith and Sesada p379)

214. Diazoxide: Stoelt 327 works in 1-2 min for 6 – 7 hrs so can’t titratea. has diuretic activity decreases GFR; NOT a diureticb. opens ATP dependent K channels we have a winnerc. not absorbed orally F = 0.80d. ? also tocolytic, inhibits insulin release, increases CO and HR

215. Phenylephrine: Stoelt 272-3a. metabolised by COMT nonb. causes mydriasis topically, yesc. metabolised by MAO weaklyd. effect lasts longer than noradrenaline Stoelt 272 e. acts by indirect method only direct acting

216. Regarding hydralazine: Stoelt 310 and ?Katzung or Peck – can’t recalla. fast acetylators have shorter half-lives than slow acetylators fast acetylators 45 min; slow

acetylators 2-3/24b. acts via SNS mechanism direct smooth muscle effectc. slow acetylators decrease half-lifed. has diuretic action RBF but UOe. clearance > 50ml/kg/min1 – 2 ml/kg/min

217. Hydralazine:a. acts via alpha 1 receptors direct smooth muscle effectb. ?c. ?d. ?e. has a duration of action of 1-2 hours too short – PD’s comment is from Stoelt 310 Comment (PD): Acts via direct effect on arteriolar smooth muscle, has a duration of action of 3-6 hours after onset of action of 10-20 minutes.

218. Concerning dobutamine:a. levo has alpha-1 antagonist and beta agonist effects nob. levo has partial alpha agonist effect and beta effects no but best of these 3c. is a pure beta agonist nod. ?Comment (PD): Dextro isomer is beta-1 agonist and laevo isomer is alpha-1 agonist. dextro: 1 - ++++ laevo 1 ++ + katzung 131D-dobutamine antagonist, L-dobutamine agonist at alpha, at beta both agonist (Bris course notes)

219. Adenosine: Stoelt 343 plus katzunga. causes AV block via action of A1 receptorsb. causes bronchoconstriction via A2 receptors A1

c. causes renal vasodilatation aff arteriolar constriction (TG feedback)d. causes profound depression of the SA node ??profonditye. decreases AV transmissionComment (PD): May cause bronchospasm but this is via A1 receptors.

220. Clonidine:a. causes hypertension and tachycardia opposite - Stoelt 306b. causes bradycardia Stoelt 306c. a single dose given orally is significantly less effective than an intravenous dose high

bioavailability – almost 1.0 – so doubtfuld. counteracts the hypertensive response in pheochromocytoma no - Stoelt 305e. ?

221. The first sign of sodium nitroprusside toxicity is:a. cyanide toxicity lateb. tachyphylaxis Stoelt 317c. hypotension desired effectd. ?

222. Dexmedetomidine: Stoelt 307a. alpha-1 antagonist 2 agonistb. ?c. decrease in intraocular pressure C prob true since clonidine decr IOP (?ref). Does cause

decreased IOP. Can’t find ref for Dex but for Clonidine ref = Sasada and Smith. This is one of the reasons they are pushing Dex for use in ICU, cause it’s good in head trauma (apparently)

d. partial alpha-2 agonist fulle. less selective than clonidine more (7 x)

223. Amiloride: Stoelt 442a. potassium sparing antidiuretic which blocks the aldosterone receptor this description is of

spironolactoneb. blocks luminal sodium channels in the collecting tubulesc. increases potassium excretion sparesd. is metabolised by the liver not metabolisede. has a short elimination half time 18 – 24/24

224. With regard to sodium nitrate in CN toxicity:a. causes methaemoglobinaemia see Q 182b. used to create more hydrocobalamin c. used to displace CN from Hbd. creates more sulphydryl groups

225. Methylxanthines: Stoelt 285, 526-7, Katzung 338a. (something about Ca currents)b. (something about K currents)c. inhibit adenosine receptors plus non-specific PDE inhibitiond. decrease plasma glucose level no ref; not true if you take sugar in your coffeee. cause diuresis by acting on renal tubules weaklyf. physically addictive ? ref F I get a headache if I haven’t had my double expresso by about

10am but someone else I’m studying with won’t accept that as proof.

Endocrine Drugs

226. Chlorpropamide: Stoelt 423, 431 - 3, Katzung 726a. inhibits ADH secretion sensitises renal tubules to low [ADH] – helpful in DIb. has a short duration of action half life 32/24 (longest acting sulfonylurea)c. increases glucose entry into cells act at islet cells, inhibiting K+

ATP channels, depolarising cell and causing insulin release

d. is prolonged in renal failure yes, as 20% excreted unchanged

227. Sulphonylureas: Katzung 724a. high incidence of lactic acidosisb. good in patients with depleted insulin storesc. metformin and phenformin are examplesd. increased glucose utilisation in the peripheriese. are related to sulphonamides Stoelt 430

228. With regard to sulphonylureas: Katzung 724

a. work effectively if insulin stores depletedb. cause a lactic acidosisc. tolbutamide, ?, phenylformin are examplesd. highly protein bound 80 – 90 % albumin bounde. ? all are weakly acidic; all apart from chlopropamide and tolbutamide exert a weak

diuretic effect; all extensively hepatically metabolised; 2nd generation (the ones starting with G) are more potent but not more efficacious

229. Glipizide is: Katzung 724, Stoelt 433a. a biguanideb. half-life 4-6 hours 12 – 24/24c. causes metabolic acidosis/lactic acidosisd. not contraindicated in hepatic failure liver disease prolongs elim half life and increases

risk of hypoglycaemia Stoelt 432e. highly bound to albuminf. is ineffective in patients with low insulin storesT1/2 7hrs, DOA 16-24hrs (either Stoelt or Rang and Dale)

D Rang and Dale has a table of the different OHG’s and says which are CI’d in renal/ hepatic failure etc. Doesn’t say hepatic for Glipizide but you would think so. Stoelt says so… examiners win again.

Miscellaneous Drugs

230. Oxytocin:a. synthetised in posterior pituitary hypothalamusb. poorly absorbed orally broken down by gut peptidasesc. metabolised by oxytocinase in the liver B&C true - metabolised by oxytocinase in the liver

and kidney (smith&sesada)d. bolus dose will increase central venous pressuree. bolus dose will increase systemic vascular resistance

231. Cisapride: Katzung 1068 – 9, Stoelt 450a. will increase gastric motility in the presence of atropine nob. can be used to treat opioid induced gastric stasisc. decreases/increases lower oesophageal sphincter tone (?due to atropine)d. decreases gastric pH no change in gastric secretione. increases gastric volume no change in gastric secretionf. blocks histamine receptors nog. agonist at D2 receptorsno

doesn’t cross BBB; works by ACh release by ENS232. Regarding the plasma half-life of heparin: Peck 299, Stoelt

a. clearance affected by warfarinb. depends on site of injection not given IM; no mention of half life SCc. less for low MW heparins >d. depends on dose given yep – also markedly increased by low temp

233. Heparin:a. has a half-life dependent on dose yes per Stoelt 453b. inactivates factors XII, XI, X, IX NB it’s the active factors that are affected - Xa first then

IXa, XIa, XIIa

c. ?d. ?

234. Paracetamol:a. has an active metabolite no

b. interferes with renal blood flow noc. does NOT cause gastric irritation Stoelt 253d. causes methaemoglobinaemia no – phenacetin doese. maximum adult dose 4g per day

235. Paracetamol: Stoelt 253 –4a. is a powerful anti-inflammatory agent nob. should never be given in a dose >20mg/kg to children noc. increased risk of hepatic necrosis in chronic alcoholics TeOh 830d. sulphate conjugation is major metabolic pathway gluc 65%; sulf 35%e. pKa 3.5 9.5f. ?glutathione conjugation glucuronide

236. Paracetamol:a. has analgesic, antipyretic and anti-inflammatory effects nob. is metabolised to n-acetyl-p-benzoquinone which is inactivated by conjugation with

glutathione yes – NB different texts call it slightly different things – this name is the easiest to remember

c. dose should not exceed 4000mg/day in an adult std dose – but not in Stoelting so I must have been dreaming all these years. Fatality reported with 15 g single dose in adult.

d. gastric irritation is common no

237. Aspirin: Stoelt 251 - 3a. at low doses inhibits prostacyclin low dose (75 – 100 mg/d) selective inhibition of TxA2

not PgI2 is the basis of its use in stroke/AMI prevention Stoelt 252b. reversibly inhibits lipo-oxygenase no effect on LOXc. irreversibly inhibits cyclo-oxygenased. can cause asthmatic reactions yes, in 8 – 20%

238. Serotonin is most common in:a. plateletsb. enterochromaffin cellsc. cerebral cortexd. pineal glande. GITf. Mast cellsComment (PD): about 90% of the body’s stores of serotonin are present in the enterochromaffin cells of the GIT. Stoelt 403

239. Mannitol: cf questions 200 - 201a. metabolised in the liver not metabb. half-life is proportional to GFR see hc. increases Na loss but as hypotonic urine lost, increases [Na] in plasmad. excretion is dependent on GFR see he. urine will be hyperosmolar compared to plasma nof. absorbed orally nog. isotonic hyperosmolarh. clearance dependent on GFR I’d like to see a ref for this – but it should be true

240. Gastric drugs, which is true?a. sucralfate is a mixture of sulphated sucrose and bismuth that sits in the ulcer no bismuthb. gastrin and acetylcholine directly and indirectly inhibit H secretion stimulatec. misoprostil decreases gastric acid and causes marked constipation diarrhoead. pirenzipine is less effective than H2 blockers Stoelting p244e. omeprazole reversibly inhibits proton pump irreversibly

241. A decrease in renal function might be expected with:a. gentamicinb. cisplatinc. busulphand. methotrexatee. all of the above

242. Thrombocytopaenia is a side-effect of which ONE of the following:a. busulphanb. cisplatinc. methotrexated. all of the abovee. ?

243. Theophylline levels increased with:a. smoking K1133 - metabolism and levelsb. phenytoin K1131 - metabolism and levelsc. cimetidine K1128 - metabolism and levelsd. ?

244. When a beta agonist binds to linked to a G-protein:

a. there is a fall in cAMP b. the signal is amplified 108 times ? ref but sounds too good not to be truec. ?

245. Dantrolene: Katzung 460, Stoelt 529 – 30, Miller 1039a. is a benzyl-isoquinoline derivative substituted hydantoinb. undergoes oxidative and reductive metabolism principally oxidative – 5 hydroxylationc. inhibits sodium channel activation nod. causes a marked reduction in contractility no, but can cause uterine atony D true –

‘decreased (skeletal) muscular contraction for a given electrical stimulus (smith&sesada) surely contractility is cardiac??

e. not effective as prophylaxis because of poor oral bioavailability is effectivef. acts via ryanodine receptor probably yes – acts to Ca release from SRComment (PD): Dantrolene is a hydantoin derivative, interacts with DHP receptor to block neural connection to ryanodine receptor. Decreases Ca release from sarcoplasmic reticulum, preventing activation of myosin ATPase and muscle contraction. Little effect on myocardial contractility. Metabolised to 5-hydroxydantrolene and also by reduction and acetylation. Only one third of oral dose is absorbed but effective prophylaxis against MH with 5mg/kg in 3-4 divided doses every 6 hours with last dose 4 hours pre-op. Muscle weakness, sedation and hepatitis. Orally for spasticity and chronic neurological disorders.

246. Dantrolenea. benzylisoquinoloniumb. undergoes hepatic and renal metabolismc. profound myocardial depressiond. poor oral bioavailability prob best of theseComment (PD): ?definition of poor.

247. Omeprazole: Stoelt 396a. irreversibly inhibits the parietal cell B better answer as it inhibits the proton pump (sure,

that’s the parietal cell’s main function but it doesn’t inhibit the cell per se.) Shades of grey loom again…

b. acts at apical membrane of parietal cell well, yes – it binds at the canaliculus – but a is a better answer

c. acts at the basolateral membrane of the parietal cell

248. Diclofenac:a. plasma protein binding is ….%b. percent absorption ….%c. mechanism of action via increase in endorphinsd. ?Comment (PD): 99% bound to serum proteins, mostly albumin, 50% first pass effect. Peak concentration 10-30 minutes. Metabolised by hydroxylation and conjugation. Elimination half-life is 1.5 hours. Clearance 3ml/kg/min agree

249. Regarding phenytoin: (which, incidentally is a hydantoin, rather like dantrolene… sense an MCQ there?) Katzung 397, Stoelt 510

a. acts via blockade of Na channels and via effect on K channels Slows inward Na and Ca flux and delays outward K flux (Sasada + Smith) I would say A

b. weak base with pKa 8.3 weak acid w this pKac. has active metabolites nod.e. ?Comment (PD): Weak acid with pKa 8.3, acts via blockade of Na channels and at concentrations in excess of 10mcM, delays the activation of outward K currents leading to an increased refractory period. Metabolites are generally inactive.

250. Which ONE of the following decrease gastric pH? a. omeprazoleb. famotidinec. calcium salts Stoelt 444 talks of rebound HCl secretion after CaCO3 which is fair enough;

I also wonder from first principles whether CaCl2 could by mass action drive the CaCO3 HCl neutralising reaction backwards to produce HCl: ie CaCl2 + 2HCO3

- 2HCl + CaCO3 (I haven’t bothered balancing the stoichiometry properly)

d. misoprostile. PGE2

251. Which one of the following decreases gastric acid secretion?a. ?b. misoprostilc. cisaprided. Na citratee. Metoclopramide

252. NSAIDS: Stoelt 247 - 258a. exhibit no selectivity for COX 1 & 2b. exert renal effects other than effect on afferent arterioles yes 250c. cause renal toxicity separate to inhibition of prostaglandins yes, papillary necrosis is

related to concentration of drug thered. aspirin and ketorolac irreversibly bind COX 1 & 2 not ketorolace. directly cause gastrointestinal ulceration can do – via Pg inhibn

253. Irreversible cardiomyopathy can be due to: Katzung 930’s…yawna. vincristine

b. bleomycinc. danorubicind. asparaginasee. cyclophosphamidef. all of the above

254. Streptokinase: Stoelt 462a. acts on circulating plasmin binds noncovalently to plasminogen, converting it to a

plasminogen activator complex that acts on other plasminogen molecules. Other plasminogen activators are in fact enzymes

b. ?c. is antagonised by aminocaproic acid (EACA) functional antagonism – binds reversibly

to plasminogen, displacing it from fibrin, so inhibiting the proteolytic effect of plasmin Stoelt 559

d. ?e. ?

255. Gastric lavage: TeOh 1090a. not useful if more than one hour has elapsed less useful, and so generally not doneb. in children, use normal saline instead of water yes, usuallyc. contraindicated if poison corrosive yes – this is prob the best answerd. is performed in the right lateral position left laterale. should not be performed in the unconscious patient without an ETTComment (KB): The restriction in unconscious patients is they should be intubated for airway protection.Comment (PD): Saline solution is safer in children because of the risk of water intoxication.

256. Long term prednisolone 2mg/day will result in:a. increased lymphocyte count acute use - lymphocytes, probably by sequestration;

chronic use get leucocytosis and increased Hct Stoelt 422b. increased capillary permeability per Katzung 665c. metabolic alkalosis hypokalaemic metab alkalosis because of mineralocorticoid effect on

DT – Stoelt 421d. ??glucose anti insulin so hyperglycaemia

257. NSAIDs cause gastric side-effects by:a. direct effects on mucosab. indirect effectsc. ?

258. Phenylbutazone: (NSAID – commonly asked useless drug, with severe toxicity issues ie anaemia and agranulocytosis limiting its use to < 7/7 – N, V, rashes, Na retention, plasma vol expansion, APO; displacement of warfarin, oral hypoglycaemics and sulfonamides from albumin; displaces thyroxine from its protein binding sites too and fucks up TFTs; decreases iodine uptake by thyroid – why would anybody consider prescribing it????) Stoelt 255, word for word.

a. interferes with heparin metabolismb. increases warfarin plasma concentrationc. decreases warfarin plasma concentrationd. reduces the elimination of warfarin

259. Phenylbutazone:a. binding to albumin, displacing warfarinb. inhibiting warfarin metabolismc. ?some interaction with aspirind. ?effect on platelets

260. With respect to prednisone:a. prednisone is converted to active prednisolone in the gut after its absorption form GIT

Stoelt 416b. prednisone 5mg is equivalent to 100mg cortisol no, pred 5 = 20 cortisolc. betamethasone has equivalent mineralocorticoid activity noned. methylprednisolone ? has very similar pharmacokinetics: 4 - 5 x antiinflamm FX of

cortisol, 0.5 mineralocorticoid, half life 2-4/24, lasts 12 – 36 hrsComment (PD): Prednisone is rapidly converted to prednisolone after its absorption from the gastrointestinal tract.

261. Aspirin:a. greatest absorption is from the stomach yes, weak acid with pKa 3.5 – so RATE of

absorption is greatest in stomach but more AMOUNT absorbed in small intestine as greater surface area

b. peak plasma level is achieved in 30 minutes 1-2 hrsc. has cross-reactivity with all NSAIDSd. half-life of 4 hours Also T1/2 for aspirin 15-20mins, Salicylic acid 2-3hrs p251. I can’t

find time to peak plasma concerntration for Aspirin (not S.Acid) but if that is T1/2, must be short, does it have time to reach SI in 10mins?

Comment (PD): Low dose aspirin elimination half life is 4 hours (salicylic acid) and elimination follow first order kinetics. With higher doses elimination follows saturation kinetics and elimination half-life is 15 hours.yep A incorrect stoelt p251 – another source says SI>stomach because ↑ SA, even though more unionized in stomachp251 Stoelt “rapidly absorbed from SI and to a lesser extent from the stomach” B/c SAAnd p253 “patients who are allergic to aspirin cross react to all inhibitors of PG synthesisC is right, A is wrong

262. Organophosphates:a. phosphorylate the esteratic siteb. phosphorylate the anionic sitec. ?d. ?Comment (PD): organophosphates combine with AChE at the esteratic site to form a stable, covalently bonded, inactive phosphorylate complex that does not undergo hydrolysis.

263. Bleomycin:a. related to nitrogen mustard cyclophos isb. can cause agranulocytosis minimal myelosuppressionc. causes pulmonary toxicity in 90% of patients 40%d. is an alkylating agent no, it’s an antineoplastic antibiotice. causes pulmonary oxygen toxicity due to production of superoxide radicals inhibits SOD

with high FIO2

264. Syrup of Ipecac:K 1016 NB only ejects 28% of liquid gastric contentsa. is not effective in phenothiazine overdoseb. has peripheral irritant and direct CTZ action TeOh 1089c. the syrup is more potent than the fluid avoid fluid – contains cardiotoxic alkaloids and

more potent apparentlyd. ?

265. Regarding antiemetics which drug has anti-5HT-3, anti H1 and anti-D2 actions?a. ondansetronb. scopolaminec. domperidone does not cross BBBd. droperidole. prochlorperazine from Bris notesf. chlorpromazine F better answer (Smith and Sesada)

I could only find D2 and H1 for Prochlorperazine. Maxalon D2, 5-HT, Ach. Now can’t find the 5-HT ref. Was sure it was Stoelt but has now disappeared

That makes Chlorprom right for all 3 versions (if it’s 5-HT3) and Maxalon also right for version 2

266. With regard to nitric oxide:Katzung 331a. it is anaesthetic at high concentration try… lethalb. may improve V/Q mismatchc. is liquid in the cylinder, gas at room temperature gasd. ?

267. Ethanol: Katzung 382 – which is best answer???????? B, d, e or f?a. about 35% excreted via the lungs 90% hepatic oxidationb. concentration falls at a fixed rate with respect to time zero orderc. only 60% metabolised, the remainder being excreted in expired air nod. is excreted at a rate independent of plasma concentration zero ordere. constant elimination independent of plasma concentration zero orderf. elimination is not dependent upon amount absorbed from GIT zero order

B – pedants would say the amount not concentration falls at a fixed rate. Pick D-FE best in my opinion but depends on the options on Monday!!268. Which drugs cause convulsant activity:

a. cocaineb. lithium fits at [Li] > 2.5 mmol/l Stoelt 368 - 9c. norpethidined. enfluranee. all of the above

269. Metoclopramide:a. increases gastric emptying faster with an oral dose than an IV dose no ref but as it has

peripheral effects this seems the best answer hereb. causes diarrhoea in children B – causes diarrhea (G&G p918) but not a specific ref to

kidsc. is a dopamine agonist antagd. ?don’t use if PHx Ca breast as increases PRL; inhibits BuChE

270. Physostigmine:a. causes excitatory activity on the EEG yes Katzung 101b. doesn’t cross the blood brain barrier does crossc. doesn’t cause sedation its ACh FX tend to stimulate – Stoelt 234d. only has its effects at nicotinic receptors N & Me. causes amnesia no ref for thisf. is a quaternary ammonium that doesn’t cross the BBB nope

271. Drugs filtered and secreted in the PCT include:a. penicillinb. probenecidc. chlorothiazided. ?

272. Which basic drug is secreted by the kidney for excretion?a. Procainamide K 231, Stoelt 334 – is basic, 40 – 60% renal excretion unchanged so surely

uses the basic secretor mechanism used by histamineb. probenecid acidc. penicillin more acid, mand. acetazolamide Acetazolamide = weak base

273. Which of the following is bacteriostatic only? Static: sulfonamides, macrolides, TMP, chloramphenicol. The reason TMP and SMX were combined in Bactrim/septrin was that the combination is cidal.

a. Penicillin Katzung 754b. Gentamicin Katzung 784

c. Vancomycin Katzung 768d. Trimethoprim Katzung 795 impliese. Cefoxitin Katzung 762

274. With respect to serotonergic receptor action, which ONE of the following is true?a. sumatriptan is a 5HT-1 antagonistb. ondansetron is a 5HT-3 agonistc. ?d. metoclopramide is a 5HT-4 agonist which is why it’s prokinetic; prokinetic effect is NOT

DA related Stoelt 448e. ?Comment (PD): Sumatriptan is a 5HT-1 agonist, ondansetron is a 5HT-3 antagonist.

275. Acetazolamide:a. ?secreted by the renal tubules yes???b. ?diuresisc. ?develop tachyphylaxis ?ref

276. Best antiemetic for motion sickness:a. metoclopramideb. ondansetronc. ?d. ?e. hyoscine acts at vestibular apparatus

277. Complications of salbutamol used in asthma treatment include the following except:a. tachycardia yesb. decreased V/Q mismatch can improve or worsenc. tremors yesd. pulmonary oedema ??? ref – I wonder if this was the answer and E was incorrectly

recalled Can’t find the pulm oedema reference anywheree. hyperkalaemia hypokalaemia – Peck 174, Stoelt 275 – also Mg and hyperglycaemia

278. Aspirin overdose: Katzung 1019 – medullary stimulation so hyperventilation; increased lactate production and increased bicarb excretion so metab acidosis

a. causes metabolic and respiratory acidosisb. causes metabolic and respiratory alkalosisc. causes metabolic alkalosis and respiratory acidosisd. causes metabolic acidosis and respiratory alkalosisDepends on age of patient and how far into the OD they are (duration). Rang and Dale: 1st resp alkalosis and then resp acidosis =/- metabolic acidosis from lactic/pyurvic acids etc. Children more likely to get met acidosis and adults more resp acidosis… Just when you thought you understood. A or D I just don’t know I would be inclined to KISS and invoke only the early and more direct effects.

279. Low molecular weight heparina. has better bioavailability >90% (30% for UFH) Bris notesb. molecular weight 1/10 that of normal heparinc. more protein bound than heparind. ?e. ?

280. Desmopressin:a. increases factor Xb. increases factor Vc. causes sustained severe hypertension not vasoconstrictord. can be used to improve haemostasis in haemophilia stims F VIII synthesis and releasee. increases factor VIII activity less accurate than D in my view

281. An intravenous infusion of 8.4% sodium bicarbonate to a healthy adult may cause: covered in KB’s viva book and in the acid-base notes on the website (section 8.7)a. hypotonicity hypertonic – causing incr BV +/- CCFb. intracellular acidosis via CO2 moving intracellularly, esp if not compensatorily

hyperventilated to offset increased CO2 productionc. ionised hypercalcaemia think carpopedal spasm (Ganong 369 and 57) – increased pH so

increased plasma protein ionisation so increased Ca2+ binding so decreased free Ca2+

d. ?respiratory alkalosis noe. rebound metabolic acidosis rebound alkalosis

282. Cyclo-oxygenase-1 (COX-1) isoenzyme:a. is increased by inflammation no, it’s constitutive COXb. is ?predominant mode of action of indomethacin best of bad lot – indomethacin does

affect it as it’s nonselectivec. in increased by lipopolysaccharide ie G –ve endotoxin – no, it’s constitutive COXd. is NOT involved in gastric mucosal protection tise. is increased by cytokines no, it’s constitutive COX

283. Caffeine: ?refsa. is a CNS depressant not in my experienceb. causes cerebral vasoconstriction yentis 83c. reduces the acidity of gastric fluid secretiond. reduces plasma glucose levele. is a potent diuretic Yentis 23f. has been shown to be dependence producing F true surely…. Maybe I need another…..

I’ll even settle for instant….g. does not show an improvement in psychomotor function

Statistics MCQs all refs to Myles and Gin

284. Tests that use ranking of data:a. can be applied to any distribution pp 63 -4b. include the chi square test 69 – categorical data onlyc. have greater power than non-ranking tests 64 less powerd. ?normal distribution nonparametric is OK

285. Standard error of the mean: = SD/(n)0.5

a. is proportional to N 9b. is greater for sample than SD of population is lessc. measures variance within a sample 9 - nod. measures dispersion around population meanComment (PD): Shows the spread of variance around a population mean.

286. Use of chi-square test inaccurate with:a. 2x2 contigency table no!!b. expected value of any cell < 5 70 - 1c. observed value of any cell < 5d. ?

287. The mean in a very large sample:a. numerically greater than the standard deviation large sample so small SD one would

expect, as SD = (((x – mean)2)/(n-1))0.5

b. is always equal to the modec. is more than the mediand. represents a normal distributione. gets larger as the sample size increases

no good answer A is incorrect as the mean may be any number, even zero! D – a large sample does represent a normal distribution

288. The standard normal distribution:a. standard deviation is one A true as well – standard normal is the z distribution (p13)b. mean, median & mode are the same 14c. mean is oned. mode is one

289. In a study for depth of epidural catheter insertion, the mean is 4.4 and the standard deviation is 0.3. Which ONE of the following is true? P 14a. if a normal distribution , 68% of values would lie between 4.1 and 4.7cm +/- 1 SD 68%,

+/- 2 SD 95.4%, +/- 3 SD 99.7%b. none was greater than 5.5cmc. the least distance was …?d. 99% of the sample lies within 1.96SD of the mean 95% doe. 500 patients had catheters at same length.

290. Simple linear regression (graph of straight line crossing y axis at +3):a. y = 3 + 6xb. y = 3 + 0.6xc. ?d. none of the above can’t interpret this – NB, though, that the line should NOT extend

beyond the limits of data, which could easily be a trap for us

291. Ordinal data:a. assumes a normal distribution nob. ?c. ?

292. Paired t-test 51a. assumes the normal distributionb. is a non-parametric test

293. In a clinical trial, a patient either vomits or not. What type of data is this? P 1 – 3 I reckon categorical would be best

a. ordinalb. nominalc. ratiod. interval

B – dichotomous categorical p1 = nominal for only two outcomescategorical aka nominal

294. Odds ratio: = ad/bc pages 74 - 75a. is prevalence vs. incidenceb. gives an indication of incidence of disease in exposed vs non-exposed patients ratio of

odds of event in active/exposed group to ratio of odds in control group when Pr(event) < 10% (overestimates risk if risk is >10%)

c. formula is number of positive outcomes/number of negative outcomesd. give the prediction of a disease outcome knowing the risk factors this is risk ratio –

(a/(a+b))/(c/(c+d))e. gives prediction of risk factors with a known disease outcome (Model answers from Bris

Course (2002) gives answer as "e")

295. With respect to 95% confidence intervals:a. equals mean +/- 1.96 SE only for large samplesb. will contain the population mean 95% of the time 23c. tells variability of sample not the main pointd. tells 5% chance of finding sample resulte. assumes a normal distribution

296. Student’s T test: 52 - 3a. used to compare 2 groupsb. used if groups have different variancec. for small size samples assumes parametric; need to be similar groups; compares meansd. ?e. ?

297. All of the following tests EXCEPT one, can all be used to compare two dissimilar groups:a. Chi square 63b. Mann Whitney U testc. Wilcoxon signed ranks sum testd. Spearman rank order by popular acclaim.e. Kruskall Wallis

I thought D since it’s the non-parametric version of correlation

No Spearman rank order is a nonparametric version of a correlation coeff. Measures association. Does not compare